My lab has two distinct interests. One focus is on the mechanisms by which cells regulate RNA processing. Genome studies have revealed that many complex organisms have fewer genes than expected. One explanation for this lies in the fact that genes often generate alternative mRNAs and thus encode multiple distinct proteins. To produce alternative mRNAs, exons must be combined in different patterns during RNA splicing in a carefully controlled way. The choice of exon sequences that are picked is regulated by both splicing activator and repressor proteins which bind pre-mRNAs and act locally to either favor or block recognition of nearby splice sites by the spliceosome. We have found that splicing repression can be carried out by some of the same proteins that cause activation. These proteins interact with each other to form similar complexes, but ultimately have opposite effects on the RNA. By investigating how these complexes interact with the pre-mRNA splicing machinery we are gaining insight into the mechanisms of splicing regulation.

A second major interest of my lab is in the development of the reproductive system. In most animals, gonads arise separately from other reproductive ducts and organs, but must fuse with them to form a continuous reproductive tract. In Drosophila we have found that fusion of the testis with the reproductive tract depends on the morphogenesis of an epithelial layer at the posterior tip of the testis. The mechanism by which this occurs is almost entirely unknown but we have found that proteins from the DM family of transcription factors play a required role. Interestingly, the DM proteins are among the only factors known to have a conserved role in sexual differentiation across the animal kingdom. We are investigating the function of these factors using genetic and molecular approaches with the goal of understanding signals that direct differentiation of the reproductive tract and coordinate organ fusion.

Recent publications

• Lazareva, A.A., Roman, G., Mattox, W., Hardin, P.E. and B. Dauwalder. (2007) A role for the adult fat body in Drosophila male courtship behavior. PLoS Genetics, 3:115–122.
  
  
• Qi, J., Su, S. and Mattox, W. (2007) The doublesex splicing enhancer components Tra2 and Rbp1 also repress splicing through an intronic silencer. Mol Cell Biol 27:699–708.
  
  
• Qi J., Su, S., McGuffin, M.E. and Mattox, W. (2006) Concentration dependent selection of targets by an SR splicing regulator results in tissue specific RNA processing. Nucl Acids Res 34:6256–6263.
  
  
• Xu, D.Q. and Mattox W. (2006) Identification of a splicing enhancer in MLH1 using COMPARE a new assay for determination of relative splicing efficiencies. Hum Mol Genet 15: 329–336.
  
  
• Unni, E., Su, S. and Mattox W. (2003) Analysis of a null mutation in the Drosophila splicing regulator Tra2 suggests its function is restricted to sexual differentiation. Genesis 37:76–83.
  
  
• Chandler, D.S., Qi, J. and Mattox, W. (2003) Direct repression of splicing by Transformer2. Mol Cell Biol 23:5174–5185.
  
  
• Dauwalder, B., Tsujimoto, S., Moss, J. and Mattox, W. (2002) The takeout gene is regulated by the Drosophila sex determination pathway and affects male courtship behavior. Genes Dev 16:2879–2892.
  
  
• Chandler DS, McGuffin ME, and Mattox W. (2001) Functionally antagonistic sequences are required for normal autoregulation of Drosophila tra-2 pre-mRNA splicing. Nucleic Acids Res. 29:3012–19.
  
  
• Du, C., McGuffin, M.E., Dauwalder, B., Rabinow, L. and Mattox W. (1998) Protein phosphorylation plays an essential role in the regulation of alternative splicing and sex determination in Drosophila. Molecular Cell 2, 741–750.
  
  
• Dauwalder B and Mattox W (1998) Analysis of the functional specificity of RS domains in vivo. EMBO J. 17, 6049–6060.
  
  
• Bauer, R., McGuffin, M.E., Mattox, W. and Tainsky, M.A. (1998) Cloning and characterization of the Drosophila homologue of the AP-2 transcription factor. Oncogene, 17: 1911–1922.
  
  
• McGuffin ME, Chandler D, Somaiya D, Dauwalder B, and Mattox W (1998) Autoregulation of transformer-2 alternative splicing is necessary for normal male fertility in Drosophila. Genetics 149, 1477–1486.
  
  
• Cooper TA and Mattox W (1997) The regulation of splice site selection and its role in human disease. Am. J. Hum. Genet 61, 259–266.
  
  
• Chandler D, McGuffin ME, Piskur J, Yao J, Baker BS, Mattox W (1997) Evolutionary conservation of regulatory strategies for the sex determination factor transformer-2. Mol Cell Biol 17, 2908–2919.
  
  
• Dauwalder B, Amaya-Manzanares FA, Mattox W (1996) A human homologue of the Drosophila sex determination factor transformer-2 has conserved splicing regulatory functions. Proc Natl Acad Sci USA 93, 9004–9009.

Last updated 07/18/2007